The regulation of adenylate cyclase was studied in nucleus caudatus, nucleus accumbens, hippocampus and cerebellar cortex of control and schizophrenic brains. The adenylate cyclase activity in the dopamine-rich brain areas of schizophrenics was more enhanced by SKF 38393, NaF or GppNHp than in similar areas of control brains. In contrast, the stimulation of adenylate cyclase by Na+ and GppNHp was similar in cerebellar cortex and hippocampus of controls and schizophrenics. It is inferred that the functional efficiency of the G/F protein that facilitates adenylate cyclase activation is increased in dopamine-rich brain areas of schizophrenic subjects. These findings suggest that aberrant dopaminergic transmission in brain of schizophrenics could be due to a basic defect in the function of the G/F protein.